Cell death and neuronal loss are the key pathological drivers of neurodegeneration in conditions such as Alzheimer's (AD), Parkinson's, Huntington's and glaucoma. AD is the commonest single form of dementia predicted to increase from affecting 4 to 12 million Americans over the next 20 years. Glaucoma is the major cause of irreversible blindness throughout the world, affecting 2% of people over 40. The condition has a significant morbidity due to its silent and progressive nature, often resulting in a delay in diagnosis and treatment.
Live cell imaging has been widely used to investigate neuronal dysfunction in cultured cells in vitro, which together with fluorescent multiple-labelling permits visualisation of different cell activities and distinct molecular localization patterns. Although in vivo imaging of the two major forms of cells death, namely apoptosis and necrosis, using radioligands have emerged in recent years (Saint-Hubert et al., 2009), until now, investigation of the progression and dynamics of the distinct phases of neurodegenerative disease at the cellular level has only depended on histological or in vitro analyses (Huerta et al., 2007).
Imaging the different phases of nerve cell death in vivo would significantly advance our ability to understand the disease and its natural history, with direct applications to the patient. It would allow investigation of the time course of events in relation to different modulators, and also provide insight into the spatial patterns of cell death over periods of days, weeks or longer. Furthermore, given the emergence of mechanistic commonalties between different neurodegenerative diseases, such as AD and glaucoma (Guo et al., 2009; Guo et al., 2007) an appreciation of the spatio-temporal dynamics of cell death in one disease could enhance our understanding of other diseases, both in terms of the molecular pathophysiology and potential therapeutic avenues. In particular, the possibility of blocking apoptotic cascade at early stages to rescue injured cells (Allen et al., 1997) makes the ability to differentiate between apoptosis and necrosis, as well as between different stages of apoptosis, particularly desirable.